Synthesis of O-Alkylated garcinol derivatives as α-amylase and α-glucosidase inhibitors

Abstract

Natural products and their semi-synthetic derivatives have become safer alternatives in treatment of Diabetic Mellitus. Garcinol, a polyisoprenylated benzophenone exhibits remarkable in-vitro anti-hyperglycemic activity with potent α-amylase and α-glucosidase enzyme inhibitory potential, which can be further enhanced through functional modifications. However, there aren’t any studies on its analogues on antidiabetic properties. Hence, the present study was aimed to synthesize the structural analogs of garcinol via O- alkylation and evaluate their in-vitro anti-hyperglycemic activity. Dried and ground fruits of Garcinia quaesita were extracted into acetone: water (9: 1) using reciprocating shaker (24x3 hours). Garcinol was isolated from the crude extract and structure was confirmed by mass spectroscopy, NMR spectroscopy, FTIR and melting point data. Four novel derivatives of garcinol were synthesized by O-alkylation using RX (C₂H₅I (product 1), CCl₃Br (Product 2), C₆H₅CH₂Br (product 3), C₇H₆BrNO₂ (product 4)) with a mild base and the products were characterized by mass spectroscopy, NMR spectroscopy and FTIR. The in-vitro anti- hyperglycemic activity was assessed by α-amylase and α-glucosidase enzyme inhibition assays. The product 1 (IC₅₀ 28.45 ±1.17 mg L⁻¹) and product 2 (IC₅₀ 34.90 ± 1.09 mg L⁻¹) showed no significance difference (p>0.05) while product 3 (IC₅₀ 71.94 ± 6.36 mg L⁻¹) and product 4 (IC₅₀ 55.27 ± 10.5 mg L⁻¹) showed significantly lower(p<0.05) α-amylase enzyme inhibitory potential compared to garcinol (IC₅₀ 37.81 ± 1.48 mg L⁻¹). The product 1 (IC₅₀12.48 ± 0.28 mg L⁻¹) and product 4 (IC₅₀ 13.92 ± 1.04 mg L⁻¹) showed no significancedifference (p>0.05) while product 2 (IC₅₀ 7.01 ± 1.61 mg L⁻¹) and product 3 (IC₅₀ 47.39 ± 2.77 mg L⁻¹) showed significant difference(p<0.05) compared to garcinol (IC₅₀ 17.18 ± 1.53mg L⁻¹) in terms of α-glucosidase enzyme inhibitory activity. These data showed that product 2 showed enhanced α-amylase and α-glucosidase enzyme inhibitory potential and it warrants further studies on in-vivo anti-hyperglycemic properties.